A fundamental challenge in tissue engineering is the nature and design of an appropriate 3D scaffold. We propose to use self-assembling peptides to engineer the 3D environment of cells with biologic functionality that can be modified and controlled, based on the basic biophysics of the material, which can be tailored for specific cell types. We employ a Partnership that brings together investigators in biophysics, bioengineering, cell biology, molecular biology, physiology, chemistry, and imaging. Team members are specialists in Electrical Engineering (Grodzinsky, PI), Mechanical Engineering (Kamm), Chemical Engineering (Griffith), Biological Sciences (Zhang, Semino, Lee-BWH), Chemistry (Klibanov) and Clinical Science (Lee, Frisbie-CSU). The use of self-assembling peptides in tissue engineering potentially enables the control of cellular adhesion, biomechanical properties, growth factor presentation and/or release, and vascularization. A fundamental theme of this Partnership is that no single tissue engineering approach is suitable for the diverse structure of all tissues. However, our central hypothesis is that by providing a physiologically appropriate, molecularly specific environment that can be modified by design, we can utilize the "core technologies" of the Partnership to improve the approach for a given tissue. This Partnership brings together expertise in several specific tissues, allowing us to interact in ways that traditional individual grants and programs do not provide. Our Specific Aims are (1) Design, & functionalization of peptide sequence of self-assembling peptides for 3D tissue engineering; (2) To explore the basic biophysics of the self-assembling peptide environment using state-of-the-art computational modeling and biophysical measurements; and (3) To explore the role of the self-assembling peptide environment in three major target tissues: myocardium, cartilage, and liver. The lead institution of the Partnership is MIT, with partners from BWH and CSU.